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European Review for Medical and Pharmacological Sciences 2007; 11: 165-170

Suppositories in anal disorders: a review


P.J. GUPTA

Gupta Nursing Home, Laxminagar, NAGPUR (India)

Abstract. – Introduction: Drug treat- creams are the two main modes of administration
ment for various ano-rectal conditions has of drugs through the rectum2.
been known since ancient times. Supposito- Suppositories are a medicated solid dosage
ries are one of the very feasible modes of ad-
ministration for medication. form intended for insertion into the body orifices.
Materials and Methods: Medline (1950- The term suppositories have its origin in Latin
2006) was searched for all published reports and means, “to place under”. It is thought that
about suppositories. This study sum up vari- suppositories were first used in nursing facilities
ous suppositories used in proctological prac- to be administered to elderly patients who were
tice, which either are in vogue and have been not capable of receiving medications through
used with a proven degree of success, or sup-
positories which are described in the literature
more traditional delivery systems3.
but are no more in use. This study attempts to In humans the rectum comprises the last 12-19
highlight the advantages and drawbacks of cm of the colon and the rectal epithelium is
each of them. formed by a single layer of columnar or cuboidal
Results: Over 30 different types of ingredi- cells and goblets cells; its surface area is about
ents have been found which are used singly or 200-400 cm2. The absorbing surface area of the
in conjugation in suppositories formulation. rectum is considerably smaller than that of the
While there are only few reports of adverse re-
action following use of suppositories like rec- small intestine, as the former lack villi and mi-
tal ulcer, rectal stricture and stenosis, the crovilli. However, the epithelium in the rectum
overall acceptance of this mode of medication and the upper intestinal tract are histologically
is good. similar, giving them comparable abilities to ab-
Conclusion: Suppositories offer to the pa- sorb drugs. The veins of the rectum comprise the
tients an option that is less invasive and less superior hemorrhoidal vein, which drains into the
discomforting. Suppositories could well be
looked as a convenient drug delivery system in
inferior mesenteric and portal system, and the
patients having ano-rectal symptoms. middle and inferior hemorrhoidal veins, which
enter the systemic venous circulation via the in-
Key Words: ternal iliac veins. However, it is a little known
Suppositories, Anal, Rectum, Proctology, Ano-rectal fact that the inferior and middle hemorrhoidal
disorder. veins bypass the liver and do not undergo first-
pass metabolism. Therefore, the drugs delivered
through suppositories to the lower and middle
hemorrhoidal veins are absorbed rapidly and ef-
fectively. The rectum is an interesting area for
drug absorption because it is not buffered and
Introduction has a neutral pH. It also has a very little enzy-
matic activity, thus enzymatic degradation does
Drugs or medications are administered not occur. The rectal mucus is more capable of
through a variety of routs, the most common be- tolerating various drug related irritations than the
ing the oral and parenteral route. While rectal gastric mucosa2.
route is less commonly used in routine practice, The ano-rectal physiology provides a suffi-
in proctological disorders it is being used effec- ciently adequate surface area for drug absorption.
tively since long1. Drugs mixed with various ad- The surface area is also permeable to non-ion-
juvant and administered through the rectal route ized drugs. Suppositories formulations are rather
do provide satisfactory pharmacokinetics with efficient in variety of different bases to increase
acceptable local tolerance. Suppositories and absorption and reduce complications4. The osmo-

Corresponding Author: Pravin J. Gupta, MS; e-mail: drpjg@yahoo.co.in 165


P.J. Gupta

sis process allows the drug to transfer from the Suppositories Containing Steroids
vehicle in the suppositories across the membrane Several glucocorticosteroids are used in rec-
of the rectum, and into the hemorrhoidal veins. tal suppositories. They include hydrocortisone
The higher the concentration and the greater the and its derivatives, diflucortolone valerate and
solubility, the more efficient is the transfer of prednisolone8. The steroids act as decongestant,
medication5. anti-inflammatory and anti pruritic agents and
Several local host factors may influence ab- in doing so they eliminate inflammation and
sorption in the rectum: the mucus layer, the vari- mucus discharge. It has been postulated that the
able volume of rectal fluid, the basal cell mem- analgesic effect of the local anesthetics is ap-
brane, the tight junctions and the intracellular parently prolonged by an increase in the thresh-
compartments may each constitute local barriers old for pain by the anti-inflammatory effect of
to drug absorption; depending on histological steroids9.
factors and on the molecular structure of the ad-
ministered drug. Suppositories Containing Astringents
Suppositories come in various sizes and The astringent causes the cells of the anal skin
shapes, which facilitates their insertion and re- to clump thereby drying the skin, which gives re-
tention in the cavity. Adult rectal suppositories lief from burning and itching.
weighed about 2 g while those for children are Some common astringents that are used in-
about half that weight. clude Hamamelis water, which is a mild astrin-
gent prepared from twigs of Hamamelis virgini-
ana. It helps in relief from the hemorrhoidal itch.
Zinc oxide 5 to 25% prevents the irritation at
Materials and Methods the perianal area by forming a physical barrier on
the skin that prevents the contact of the irritated
Medline (1950-2006) was searched for all skin with aggravating liquid or stool from the
published reports using the key words “Supposi- rectum.
tories, anal, hemorrhoids, rectum and proctol-
ogy”. This study sum up various suppositories Vasoconstrictors in Suppositories
used in proctological practice, which either are in Hemorrhoidal cushions contain swollen blood
vogue and have been used with a proven degree vessels. The vasoconstricting agents can help in
of success, or suppositories which are described relieving symptoms of hemorrhoids. On applica-
in the literature but are no more in use. The study tion, these drugs cause the blood vessels to
attempts to highlight the advantages and draw- shrink, thereby reducing hemorrhoidal conges-
backs of each of them. The suppositories used tion. These products additionally contain mild
for inflammatory and irritable bowel disease, form of anesthetic, which helps in relieving pain
malignancy and systemic infection have been ex- and itching10.
cluded. The commonly used vasoconstrictors are:
Ephedrine sulfate 0.1 to 1.25%, Epinephrine
Suppositories Containing 0.005 to 0.01% and Phenylephrine o.25%.
Local Anesthetics agents
The local anesthetics act by numbing the nerve Protectants in Suppositories
endings and provide temporary relief from pain Passing hard and dry stool is the most traumat-
and itching. These act by causing a reversible ic experience in patients having anal pathology
block to conduction in the sensory nerves. These as it results in tearing of the skin around the
are well absorbed from the mucus membrane and anus, as also in tearing and cracking which ends
used as surface anesthetics6. These provide good in bleeding. Again, when this tender skin comes
relief from discomfort encountered in cases of in contact with liquid or stool, it causes the skin
strangulated hemorrhoids, fissures and perianal to further itch and burn.
hematomas7. Protectants, when applied in the form of sup-
Some commonly used local anesthetics are: positories, form a physical barrier on the skin
Benzocaine 5 to 20%, Lidocaine 2 to 5%, Cin- and results in reducing the pain quotient and the
chocaine, Dibucaine 0.25% to 1%, Dyclonine pruritus. These also protect the broken skin from
0.5% to 1%, Pramoxine 1% and Tetracain 0.5 to coming in contact with offending particles in the
5%. stool.

166
Suppositories in anal disorders: a review

While a variety of protectants are used in sup- wound area and thereby stimulates regeneration
positories, a few commonly used are: Aluminium and re-epithelization process. It also has a an-
hydroxide gel11, Glycerin, Lanolin, Aloe vera, timicrobial property which guards against infec-
White petrolatum, Zinc oxide and Calamine. tion and prevents inflammation. Policresulen also
has astringent property and thus it suppresses
Use of Antiseptics in Suppositories oozing13.
Being a highly contaminated area, the anal and
perianal skin are susceptible to variety of organ- Other Ingredients in Suppositories
isms, which can lodge there either from the ad- Imiquimod containing suppositories have been
joining area or from the contaminated stool. The successfully used to prevent recurrence of anal
chances of contamination further increase when condylomata14. Trimebutine, an anal sphincter re-
the skin gets bruised during defecation. laxant, has been used to relieve post hemor-
Antiseptics are used to keep the area clean and rhoidectomy pain 15. Ketoprofen suppositories
to prevent infection. The commonly incorporated were recommended in patients after anal
antiseptics include: Benzalkonium chloride, surgery16.
Boric acid and Framycetine sulphate. A sedative cryotherapy was being used with
the intention of producing tissue hypothermia,
Use of Keratolytics in Suppositories giving cool numbing effect over the
Certain chemicals cause the outer layers of hemorrhoids17. Promethazine suppositories were
skin and other tissues to disintegrate when ap- proposed for hemorrhoidal complications while
plied. They eventually help in better penetration trichloroacetic acid was used for the treatment of
in the tissues of other medications contained in anal fissures18. A compound Carraghenates sup-
the suppositories to bring quicker relief. The two positories has been shown to be useful in the
commonly used keratolytics are: Aluminium treatment of mixed hemorrhoids19.
chlorhydroxy allantoinate 0.2 to 2% and Resorci- Few old references have described use of
nol 1 to 3%. Roinal 20 , Glycofuranoside derivatives 21 ,
Indacine 22, Prothanon 23, Rhubarb and Aloe 24,
Use of Calcium Dobesilate in Suppositories Phenylindanedione25, Proctoglivenol in supposi-
Calcium dobesilate is a veno-tonic drug, tories forms26. However, they are no more in use.
which is widely prescribed for three main indica- The various ingredients in suppositories form
tions: chronic venous disease, diabetic retinopa- with their use; adverse effects and contraindica-
thy and the symptoms of hemorrhoidal attack12. tions for their use have been elaborated in Tables
The drug acts on the endothelial layer and base- I and II.
ment membrane of the blood capillaries. It re-
duces capillary hyperpermeability by increasing Insertion Technique of Suppositories
the activity of endothelial nitric oxide synthase in It has been suggested that the suppositories
vascular endothelial cells, leading to an increase should be inserted with the patient lying on the
in nitric oxide synthesis. Along with Calcium left lateral side with the right knee bent. The
dobesilate, the suppositories usually contain local suppositories should be dipped in water before
anesthetic, steroid and astringent in addition use, which facilitates the easy insertion of the
[Smuth suppositories from Aristo Pharmaceuti- suppositories. It should be kept in cold water or
cals, Mumbai, India]. refrigerator for half an hour before use if the
suppositories are too soft to be inserted, espe-
Suppositories Containing Policresulen cially during warm weather. Emptying of bow-
Policresulen is a polymolecular organic acid. el should be avoided for at least an hour after
It coagulates necrotic or pathogenically altered insertion of the suppositories to allow it to be
tissue in anorectal disorder and promotes desqua- fully absorbed.
mation of such tissues. The healthy tissues sur- Although, it is a practice to introduce the ta-
rounding the wound are not affected. As a local pering end of the suppositories first and the base
hemostatic, Policresulen coagulates blood pro- at last, one randomized study has found that the
teins thereby inducing muscle fibers of small retention rate was higher and spontaneous expul-
vessels to contract and thus any hemorrhage in sion rate was lower when the suppositories was
the anal canal or in the perianal area could be introduced with “base first” technique27. It was
controlled. It also induces hyperemia in the postulated that reversed vermicular contractions

167
P.J. Gupta

Table I. Ingredients in suppositories, their uses and adverse effects.

Ingredients Indications Contraindications Adverse effects

Local anesthetics Anal pain due to strangulated Know sensitivity to Local irritation and anal
(Lignocain, Cinchocain, hemorrhoids, anal fissure, these agents cryptitis or proctitis.
Centbucridine) and post anal surgery.
Steroids
(Hydrocortisone, Hemorrhoids, anal fissures, Infective lesions like anal , Systemic absorption
Prednisolone) pruritus ani fistula abscess and cryptitis. on prolonged use
Astringents [Hamamelis Anal cryptitis, pruritus ani, Known sensitivity Local reaction
water, Zinc oxide, hemorrhoids
Allantoin)
Vasoconstrictors Hemorrhoids, hemorrhoidal Known sensitivity Headache, flushing,
[Phenylephrine] thrombosis. tachycardia.
Protectants and Hemorrhoids, anal fissures, Known sensitivity No specific adversity
Emollients pruritus ani
(Aloe vera, Zinc oxide,
Calamine)
Antiseptics (Boric acid, Proctitis, anal cryptitis, Known sensitivity Pruritus, local irritation
Benzalkonium chloride, anal fissures and burning
Framycetine sulphate)
Keratolytic Anal fissures, Known sensitivity, Skin excoriations,
(Aluminium Anal rhagades inflammatory bowel mucosal ulcerations.
Chloride, Resorcinol) disease, pregnancy
Calcium dobesilate Bleeding hemorrhoids, Known sensitivity, Agranulocytosis
hemorrhoidal attack pregnancy
Policresulen Hemorrhoids, anal fissures, Inflammatory bowel Local allergic reactions
infective anal lesions. disease

or pressure gradient of the anal canal might have of pain in the pediatric, obstetrical and general
been responsible for this finding. It was also sug- surgical practice. However, reports are available
gested that a “torpedo-shaped” suppositories where these suppositories have caused complica-
should be designed which would have a better tions like rectal and anal ulcerations 28, rectal
acceptability and efficacy. stricture29, anal stenosis, proctitis30 and peri-rec-
tal cellulites31.
Complications Following Use Systemic absorption of topically applied
of Suppositories steroids can occur in children32.
Suppositories containing non-steroidal anti-in- Calcium dobesilate is known to cause agranu-
flammatory drugs are commonly used for relief locytosis33,34.

Table II. Suppositories for various ano-rectal pathologies

Pathology Ingredients in suppositories

Bleeding hemorrhoids Astringents, vasoconstrictors, protectants, Calcium dobiselate and Policresulen


Hemorrhoidal thrombosis Local anesthetics, vasoconstrictors and Calcium dobiselate
Anal fissure Local anesthetics, steroids, protectants, antiseptics, keratolytics and Policresulen
Pruritus ani Steroids, astringents and protectants
Anal cryptitis and proctitis Local anesthetics, astringents and antiseptics
Anal rhagades Keratolytic, antiseptics and policresulen
Post anal surgery Local anesthetics, vasoconstrictors, antiseptics and Calcium dobiselate

168
Suppositories in anal disorders: a review

Discussion may be required to educate patients on proper


suppositories administration.
Drug treatment for various ano-rectal condi- In conclusion, rectal administration is yet to be
tions has been known since ancient times. Today, truly explored as a potential drug delivery sys-
modern as well as traditional drugs are being in- tem, particularly for drugs that are either too irri-
creasingly used in proctology practice. Rectal tating for the gut or are more effective when not
route with local or general effects is an interest- metabolized by the liver. Suppositories offer pa-
ing possibility of a treatment modality. Easy use tients an option that is less invasive and less dis-
and rapid absorption are two major advantages of comforting. Suppositories could well be looked
these therapeutic options4. as a convenient drug delivery system in patients
Suppositories are a very feasible mode of ad- having ano-rectal symptoms.
ministration for medication. The medicament is
incorporated into a base, which either melts at
body temperature or dissolves in the mucus se-
cretions and exerts localized or systemic action. References
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